Podoplanin expression in advanced atherosclerotic lesions of human aortas
Podoplanin expression in advanced atherosclerotic lesions of human aortas
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DOI：
10.1016/j.thromres.2012.01.003
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发表时间：
2012-04-01
影响因子：
7.5
通讯作者：
Asada, Yujiro
中科院分区：
文献类型：
--
作者：
Hatakeyama, Kinta;Kaneko, Mika Kato;Asada, Yujiro
动脉粥样硬化斑块破裂形成血栓是心血管事件的一个重要机制。PodoPlanin(Aggrus)是C型凝集素样受体2(CLEC-2)的内源性配体，表达于多种肿瘤细胞表面，参与肿瘤细胞诱导的血小板聚集及其趋化作用。泊多拉宁也在淋巴管内皮细胞中表达，有助于血管/淋巴管的分离。然而，泊多普宁在动脉粥样硬化病变中的表达尚未被研究。为了阐明泊多普宁在动脉粥样硬化病变中的表达，并评估其在心血管事件发生中的重要性，我们从31例尸检病例中检测了腹主动脉中泊多拉宁的表达。免疫组织化学分析显示泊多普宁定位于平滑肌细胞和巨噬细胞。此外，与早期由平滑肌细胞和少量巨噬细胞组成的病变相比，含有坏死核、大量巨噬细胞和平滑肌细胞的晚期动脉粥样硬化病变的泊多普宁免疫反应增强。此外，Western-Blot和Real-Time-PCR分析显示，与早期病变相比，晚期动脉粥样硬化病变中泊多普宁的表达显著增强。这些结果表明，泊多拉宁参与了动脉粥样硬化晚期的血栓形成特性，它可能是抗血栓药物的一个新的分子靶点。(C)2012爱思唯尔有限公司。保留所有权利。
Thrombus formation on disrupted atherosclerotic lesion is a key mechanism of cardiovascular events. Podoplanin (Aggrus), expressed on the surface of several tumor cells, is an endogenous ligand for C-type lectin-like receptor 2 (CLEC-2), and is involved in tumor cell-induced platelet aggregation and itsmalignant potency. Podoplanin, which is also expressed in lymphatic endothelial cells, facilitates blood/lymphatic vessel separation. However, podoplanin expression in atherosclerotic lesion has not been investigated. To clarify podoplanin expression in atherosclerotic lesion and to assess its importance for the onset of cardiovascular events, we examined podoplanin expression in abdominal aortas obtained from 31 autopsy cases. Immunohistochemical analysis indicated that podoplanin was localized to smooth muscle cells and macrophages. Moreover, podoplanin immunoreactivity was increased in advanced atherosclerotic lesions containing necrotic core, many macrophages and smooth muscle cells, compared with early lesions composed of smooth muscle cells and small numbers of macrophages. Furthermore, Western-blot and real time-PCR analyses showed that podoplanin expression was significantly enhanced in advanced atherosclerotic lesions, compared with early lesions. These results suggest that podoplanin contributes to thrombotic property of advanced stages of atherosclerosis and that it might be a novel molecular target for an anti-thrombus drug. (C) 2012 Elsevier Ltd. All rights reserved.